Pancreatic polypeptide [PP] is released from pancreatic endocrine cells following feeding. The release of this peptide from the pancreas:, produces a reduction in pancreatic exocrine secretion, as well as changes in gastrointestinal secretion and motility. PP action on digestion has been difficult to explain in that its acute actions on digestive functions are not direct. Intact vagal efferent innervation is required for PP effects, a fact that lead to speculation that PP may control vagal efferent projections to the gut and pancreas through endocrine action on brainstem structures. This view recently received significant reinforcement with the finding that the dorsal vagal complex in the medulla contains a high concentration of saturable and specific receptors for PP. Thus, pancreatic polypeptide [PP] may represent a unique digestive endocrine feedback control signal which directly regulates the excitability of vago-vagal reflex circuits to control digestive functions. We plan to apply two separate methods to test this hypothesis directly. First, we will apply PP directly to the dorsal vagal complex using quantitative micropressure injection techniques. This will establish if PP can act via vago-vagal reflex circuits to produce measurable changes in gastrointestinal and/or pancreatic functions. Studies will be performed in both anesthetized and acute, awake preparations. Next, we will determine how PP affects the function of neurophysiologically identified neuronal components of vago-vagal circuits in the brainstem in the intact, anesthetized rat. These studies will determine how PP acts on individual identifiable neuronal components of digestion control reflexes. Together, these studies will provide an indication of how this unique pancreatic endocrine hormone can control an array of digestive functions by acting on vagal circuits in the brainstem.